19-alkylidene-delta4-3, 20-keto pregnanes



United States Patent Office 3,275,622 Patented Sept. 27, 1966 3,275,62219-ALKYLIDENE-A -3,2O-KETO PREGNANES Albert Bowers, Mexico City, Mexico,assignor to Syntex Corporation, Panama, Panama, a corporation of PanamaNo Drawing. Filed Dec. 18, 1963, Ser. No. 331,386 40 Claims. (Cl.260-23955) The present application is a continuation-in-part of my US.patent applications Serial Nos. 208,603, filed July 9, 1962, and262,238, filed March 1, 1963, both now abandoned.

The present invention relates to novel cyclopentanophenanthrenederivatives and to a process for the production thereof.

More particularly, the present invention relates to novel 19-methylene-A-pregnene-3,20-dione derivatives to novel l9-met-hylene derivatives ofcortical hormones, and to the corresponding wot-derivatives thereof.

The novel compounds of the present invention are represented by thefollowing formulae:

In the above formulae R represents hydrogen, hydroxyl or a hydrocarboncarboxylic acyloxy group of less than 12 carbon atoms; T representshydrogen, ot-hydroxy, aacyloxy, a-methyl or ,B-methyl; T and R togetherrepre sent the group at the 16u,17a-position wherein R and R eachrepresents hydrogen or a lower hydrocarbon residue of up to 8 carbonatoms, which may be saturated or unsaturated, of straight, branched,cyclic or cyclic-aliphatic chain, or aromatic, such as methyl, ethyl,isopropyl, phenyl, toluyl, methylcyclohexyl and the like; R is hydrogen;OR and T together represent the group wherein R and R have the samemeaning as defined hereinbefore; R represents hydrogen or a hydrocarboncarboxylic acyl group of less than 12 carbon atoms; Y represents a ketogroup or a fl-hydroxyl; and X represents hydrogen or a lower alkylgroup.

The acyl groups are derived from hydrocarbon carboxylic acids containingless than 12 carbon atoms which may be saturated or unsaturated, ofstraight, branched, cyclic or cyclic-aliphatic chain, aromatic and maybe substituted by functional groups such as hydroxy, alkoXy containingup to 5 carbon atoms, acyloXy containing up to 12 carbon atoms, nitro,amino or halogen. Typical ester groups are the acetate, propionate,enanthate, benzoate, trimethylacetate, t-butylacetate, phenoxyacetate,cyclopentylpropionate, aminoacetate, and fi-chloropropionate.

The compounds represented by Formulae A and C are powerfulprogestational agents with good oral activity. In addition they haveanti-androgenic, anti-gonadotrophic and anti-estrogenic properties andare very useful in fertility control. Furthermore, they may be: used inthe treatment of premenstrual tension and exhibit blood cholesterollowering and diuretic activities. When applied topically, thesecompounds are very useful in the treatment of acne.

The compounds represented by Formulae B and D are valuable corticalhormones with high anti-infiammatory, low catabolic, glycogenic andthymolytic activities. In addition, they are anti-androgenic,anti-gonadotrophic and anti-estrogenic hormones. Furthermore, they havehigh topical activity in skin disorders, such as psoriasis, allergicdermatitis and the like.

The novel compounds of the present invention are prepared by the processillustrated by the following formula scheme:

on CH3 IQ r5,

In the above formulae R R R T and X have the same meaning as set forthhereinbefore; 2 indicates that C-19 may have a or B configuration.

In proceeding in accordance with the above scheme, the starting compound(I), which is a 3,20-biscycloethylenedioxy-A -pregnen-19-al or theIlla-derivative thereof is treated with triphenylphosphonium lower alkylbromide such as triphenylphosphonium methyl or ethyl bromide, in thepresence of butyl lithium in a solvent inert to the reagents, such asether, under anhydrous conditions, thus affording the corresponding3,ZO-bis-cycloethylenedioxy- 19-methylene-A -pregnene derivative (11).The cycloethylenedioxy groupings of the latter compound areconventionally hydrolyzed in an acid medium to produce the corresponding19-methylene-A -pregnene-3,20-dione derivatives (III). The19-methylene-A -pregnene-3,20- dione derivatives having an hydroxyl atC-17a (II: R H), are treated with iodine, in the presence of calciumoxide, to give the corresponding 21-iodo derivatives, which uponreaction with potassium acetate in a suitable solvent, such as acetone,under anhydrous conditions, yield the corresponding l9-methylene-A-pregnen-21-ol-3,20- dione acetate (IV). The latter 21-acetoxy compoundsupon incubation with adrenal glands in a suitable medium, e.g. anaqueous solution of alkali metal phosphates and chlorides and magnesiumsulfate, mixed with an aqueous solution of fumaric acid and sodiumhydroxide for a period of time of the order of 3 hours, at approximately30 0., followed by conventional acetylation in pyridine with aceticanhydride, yield the corresponding 21-acetoxy- 11fi-hydroxy-19-methylenederivatives (V), which upon oxidation, preferably with Jones reagent,afford the corresponding 11-keto derivatives (VI).

The compounds of the present invention having a 16a,17a-ketonidegrouping, yield the corresponding 16a, l7oa-diOlS by conventionaltreatment with a strong acid, such as formic acid. The obtained diols,upon conventional esterification in pyridine with an acylating agent, asfor example acetic anhydride or caproic anhydride, afford thecorresponding 16-acylates.

The latter 16u,17ot-diols upon conventional condensation with a ketoneor aldehyde, such as benzaldehyde, acetophenone, methyl-ethyl ketone,acetone, and the like, in the presence of an acid, yield thecorresponding 160a, Hot-methylenedioxy derivatives, wherein thesubstituent in the methylenedioxy group may be different from those ofthe previously hydrolyzed ketonide grouping.

The compounds of the present invention having a 21- acyloxy group, aresaponified by conventional treatment with a base to produce thecorresponding 21-free alcohols which in turn may be acylatedconventionally in pyridine with an acylating agent to give thecorresponding 21- acylates, wherein the acyl group may be different fromthe previously saponified one. I

The compounds of the present invention having a 1741- hydroxy group areesterified conventionally in the presence of p-toluenesulfonic acid withan acylating agent, such as acetic anhydride, thus affording thecorresponding 17a-acyloxy derivatives.

The following specific examples serve to illustrate but are not intendedto limit the scope of the present invention:

PREPARATION 1 A mixture of 5 g. of A -e-pregnen-19-ol-3,20-dione(obtained according to Cross US. patent application Ser. No. 231,831,filed Oct. 19, 1962, now Patent No. 3,206,459), from the corresponding A-pregnen 19-ol-3,20- dione, by hydrogenation of the A double bond,tosylation of the resulting allopregnan-l9-ol-3,20-dione, treatment ofthe obtained l9-tosylate with sodium hydride, hydrolysis of theresulting 2,19-cycloallopregnane-3,20-dione in a strong acid or basicmedium and finally introduction of a A -double bond into the obtained10u-allopregnan-19- ol-3,20-dione by conventional procedures, i.e.successive treatment with bromine, sodium iodide and 'y-collidine, 150cc. of anhydrous benzene, 60 cc. of ethyleneglycol distilled over sodiumhydroxide and 800 mg. of p-toluenesulfonic acid monohydrate was refluxedfor 12 hours with the use of an adapter for the continuous removal ofthe water formed during the reaction. Aqueous sodium bi :arbonatesolution was added to the cooled mixture and :he organic phase wasseparated, washed with water, iried over anhydrous sodium sulfate andevaporated to Crystallization from acetone-hexane afforded3,20-biscycloethylenedioxy-A -10a-pregnen-19-al.

By the same procedures, the starting compounds listed below under A,obtained according to the aforesaid patent application, wererespectively converted into the products set forth hereinafter under B:

3,20-bis-cycloethylenedioxy 16amethyl-A -10a-pregnen-19-al.

3,20-bis-cycloethylene-dioxy-ltiflmethybA -loa-pregne11-19-211.

8,ZO-bis-eycloethylene-dioxy-N- lOa-pregnen-17et-ol-19-al.

3,20 1)is-cycloethylene-dioxy-IGB- metIhyI-A -lOa-pregnen-17a-01- 19-a-d1one. HEB-methyl-N-10a-pregnen-19-al-3,

20-dione. 16a,17a-isopropylidene-dioxyA IOwpregnen-I9-al-3,20dione.

A -1Oa-pregnene-17a,19-diol-3,20-

dione 16m-methyba -lOa-prcgnene-17a,

l9-di0l3,20-dione.

165-methyl-A -10a-pregnene-17a,

l9-diol-3,20-dione.

PREPARATION 2 A solution of 0.17 g. of potassium hydroxide in 0.2 cc. ofwater and 2.5 cc. of methanol was added over 30 minutes to a boilingsolution of 1 g. of 3,20-bis-cycloethylenedioxy-A -pregnen-17u-ol-19-al17 acetate (obtained in accordance with my copending US. patentapplication Ser. No. 201,797, filed June 12, 1962, W abandoned, bysubjecting A -pregnene-3B,17a,19-triol-20-one 17-acetate, described inmy US. Pat. No. 3,065,228 to oxidation under Oppenauer conditions toproduce A pregnene-17a,19-diol-3,20-dione 17-acetate, which is thenreacted with ethyleneglycol in the presence of p-toluenesulfonic acid toform the 3,20-bis-cycloethylenedioxy- A -pregnen-17a,19-diol 17-acetatecompound followed by oxidation with chromium trioxide) in 30 cc. ofmethanol under an atmosphere of nitrogen. Boiling was continued for afurther 2 hours and the solution was then cooled, neutralized withacetic acid and concentrated under reduced pressure. Addition of water,followed by crystallization of the precipitate solid from acetonehexane,produced 3,20-bis-cycloethylenedioxy-A -pregnen-1704-01-19- al.

Following the same procedure there were treated: 3,20-bis-cycloethylenedioxy 16a methyl-A -pregnen-l7a- 01-19-211l7-acetate and 3,20-bis-cycloethylenedioxy-- methyl-A-pregnen-1711-01-19-al 17-ace-tate, (obtained in accordance with theaforesaid patent application), thus yielding respectively:3,20-bis-cycloethylenedioxy-16amethyl-A -pregnen-l7a-ol-19-al and3,20-bis-cycloethylenedioxy-l6,8-methyl-A pregnen-17u-0l-19-al.

Example I then added dropwise in the course of 15 minutes andwithstirring. The reaction mixture was stirred for 6 hours further and letstand at room temperature over night. The ether was displaced with drytetrahydrofuran by distillation and then refluxed for 8 hours. It wasthen cooled, diluted with water and extracted several times with ethylacetate, the organic extract was washed with water, dried over anhydroussodium sulfate and evaporated to dryness. Chromatography of the residueand recrystallization of the solid eluates from acetone-hexane gave 3,20bis-cycloethylenedioxy-l9-methylene-A -pregnene (compound No. 1).

The starting compounds listed under I (which were obtained in accordanceeither with the aforesaid US. patent application or with Preparation 2)were treated by the same procedure thus affording the correspondingproducts set forth under II.

Com- I pound II ,ZO-bis-cycloethylenedioxy- 23,QO-bis-eycloethylcnedioxy- 16a-methyl-A -pregncn-lQ-al.IQ-methyIene-IGa-methyl- A -pregnene. 3,20-bis-cycloethylenedioxy- 33,20-bis-eycloethylenedioxy- 1tie-methyl-N-pregnen-19-al.19-methylene-16B-methyl- A -pregnene. ,20bis-cyclethy1enedioxy- 43,QO-bis-cycloethylenedioxy- 16a,17a-isopropylidenedi-19-11161;l1y1QI1G-16a-l7oc-1SO- oxy A -pregnen-l -al.propylidenedioxy-N-pregnene. ,ZO-his-cycloethylenedioxy- 53,20-biscycloethylenedioxy- A -pregnen-17a-0l-19-al.IQ'mIithyIene-N-pregnen- 17r1-0 3,20-bis-cveloethylcnedioxy- 63,20-bis-cycloethylenedioxy- 16u-methyl-M-pregnen-170t- Isl-methylenelfiwmethyl- 01-19-211. A -prognendia-ol. 3,20-bis-cyeloethylenedloxy- 73,20-bis-cye1oethylenedioxyl6flethyI-A -pregnen-Ua-19-methylencdofimethyl- 0l-19'al. A -pregnen-17u-01.

Example II The starting compounds of Example I were treated inaccordance with the procedure described in that example, except thattriphenylphosphoniuim methyl bromide was substituted bytriphenylphosphonium ethyl bromide thus giving respectively thefollowing final products Cpd. No.:

8. 3,20-bis-cycloethylenedioxy-19-ethylidene-A pregnene,

9. 3,20-bis-cycloethylenedioxy-19-ethylidene-16amethyl-A -pregnene,

10. 3,2.0-bis-cycloethylenedioxy-19-ethylidene-16(3- methyl-A -pregnene,

1 1. 3,20-bis-cycloethylenedioxy-19-ethylidene-16a,

17a-isopropylidenedioxy-M-pregnene,

12. 3,20-bis-cycloethylenedioxy-19-ethylidene-A pregnen-17a=ol,

13. 3 ,20-bis-cycloethylenedioxy-19-ethylidene-16amethyl-A-pregnen-1704-01,

14. 3,20-bis-cycloethylenedioxy-19-ethylidene-16B- methyl-A -pregnen-17aol.

Example III A solution of 5 g. of compound No. 1 in 250 cc. of acetonewas treated with 1 cc. of concentrated hydrochloric acid and the mixturekept at room temperature overnight. It was then poured into water,extracted with methylene chloride and the organic extract washed withwater to neutral, dried over anhydrous sodium sulfate and evaporated todryness. Crystallization from acetonehexane gave 19-methylene-A-pregnene-3,20-diode (Cpd. No.

The compounds Nos. 2 to 14, inclusive, were treated by the sameprocedure, thus aifording respectively C-pd. No:

16. 19-methylene-16a-methyl-A -pregnene-3,20-

dione,

17. 19-methylene-16fi-methyl-M-pregnene-3,20-

dione,

18. 19-methylene-l6a-17ot-isopropylidenedioxyA pregnene-3,20-dione,

19. 19-methylene-A -pregnen-17a-ol-3,20-dione,

20. 19-methylene-16ot-methyl-A -pregnen-1711-01- 3,20-dione,

21. 19-methylene-16B-methyLA -pregnen-I7 a-ol- 3,20-dione,

22. 19-ethylideneA -pregnene-3,2O-dione,

23 19-ethylidene-16ot-methyl-A -pregnene3 ,20-

dione,

24. 19-ethylidene-16B-methyl-A 'pregnene-3,20-

dione,

25. 19-ethylidine-16a,17ot-isopropylidenedioxy-M- pregnene-3,20-dione,

26. 19-ethylidene-A -pregnen-17a-ol-3,2O-dione.

27. 19-ethylidene-16a-methyl-A -pregnen-17ot-ol- 3,20-dione,

28. 19-ethylidene-165-rnethyl-A -pregnen-17ot-ol 3,20-dione.

Example IV A cooled solution of 4 g. of19+methylene-16a,17aisopropylidenedioxy-A -pregnene-3,ZO-dione (Cpd. No.18) in 30 cc. of tetrahydnofuran and 18 cc. of methanol was treatedunder continuous stirring with 6 g. of pure calcium oxide, in smallportions, and then with 6 g. of iodine. The stirring was continued atroom temperature until the solution turned pale yellow. The mixture waspoured into ice water containing 18 0c. of acetic acid and 2 g. ofsodium thiosulfate. After stirring for 15 minutes the solution wasdecanted and the precipitate was collected by filtration, thus givingthe corresponding 21-iodo derivative.

This compound was mixed with cc. of acetone and 12 g. of recently fusedpotassium acetate and the mixture was refluxed for 8 hours, concentratedto a small volume, diluted with water and extracted with ethyl acetatethe extract was washed with water, dried over anhydrous sodium sulfateand concentrated until crystallization started. The precipitate wascollected and crystallized from methanol-water, thus yielding19-methy1ene-16u, 17 a-isop-ropylidenedioxy-M-pregnen-21-ol-3,20-dioneacetate (Cpd. No. 29).

The compounds Nos. 19, 20, 21, 2.5, 26, 27 and 28, were treated by thesame procedure, thus affording respectively Cpd. No.:

30. 19-methylene-A -pregnene-17a,21-diol-3,20-

dione 21-acetate,

3 1. 19-methylene-16a-methyhA -pre gnene-1711,21-

di=ol-3,20-dione 21-acetate,

32. 19-methylene-16B-methyl-A -pregnene-17a,21-

diol-3,20-dione 21-acetate,

33. 19-et2hylidene-160-17et-isopropylidenedioxy-Apregnen-21-ol-3,20-dione acetate,

34. 19-ethylidene-A -pregnene-17oc,21-diol-3,20-

dione-21-acetate 35. 19-ethylidene-16ot-nrethyl-A -pregnene-17ot,21-

diol-3,20-dione 21-acet ate,

36. 19-ethylidene-16B-methyl-A pregnene-17ot,21-

diol-3,20-dione 21-acetate.

Example V The following solutions A, B and C were prepared usingdistilled water as solvent: solution A was prepared by mixing 425 cc. ofa 1.742% dipotassic phosphate solution (Kai-IP0 with 75 cc. 011.38%monosodic phosphate; solution B was prepared by diluting a mixture of 11t. of 4.5% sodium chloride solution, 40 cc. of a 5.75% potassiumchloride solution and 10 cc. of a 10.1% magnesium sulfate, to a volumeof 5 1t. solution C was prepared by dissolving 20.9 g. of fumaric acidand 14.4 g. of sodium hydroxide in 1 1t. of water and diluting thesolution to 1.2 It. Then 475 cc. of solution A, 4.32 lt. of solution Band 1.2 Ilt. of solution C were mixed.

Adrenal glands of recently slaughtered cattle, defatted, were ground ina meat grinder until a homogeneous mass was obtained; to 1 kg. ofhomogenate was added 2 liters of the mixture of A, B, and C solutionswith vigorous stirring. To the mixture there was then added 1 g. ofcompound No. 29, dissolved in 5.35 cc. of propyleneglycol, the mixturewas stirred at 28-37 C. for 3 hours, 13 liters of acetone were added andthe mass was stirred at room temperature for an additional 1 hour.

The acetone extract was separated by filtration, the ground adrenalswere washed with 6 liters of acetone, the extracts were combined and thesolvent removed by distillation under reduced pressure. Chromatographyon alumina and crystallization of the solid fractions afiorded 19methylene-16a,17a-isopropylidenedioxy-M-pregnene-11fi,'21-diol-3,20-dione ZI-acetate (Cpd. No. 37).

The compounds Nos. 30 .to 36, inclusive, were treated under the sameconditions, thus yielding respectively Cpd. N o:

38. 19-methylene-A -pregnene-11/3,17a,21-triol- 3,20-dione ZI-acetate,

39. 19-methylene-16a-methyl-A pregnene- '11,8,17a,21-triol-3,20-dioneZI-acetate,

40. 19-methylene-l 6,8-methyl-A -pregnene- 11,8,17u,21-triol-3,20dione21-acetate,

41. 19-ethy1idene-16a,17u-isopropylidenedioxy- A-pregnene-11;3,21-diol-3,20-dione ZI-acetate,

42. 19-ethylidene-A -pregnene-1 1p,17a,21-triol- 3,20-dione 2'1-acetate,

43. 19-ethylidene-16a-methyl-A -pregnene- 1 1 {3,17a,21-triol-3,20-dione21-acetate,

44. 19 ethylidene-1 6B-methyl-A -pregnene- 11,6,17oz,21-triOl-*3,20-dine21-acetate.

Example VI A solution of 1 g. of compound No. 37 in 10 cc. of acetonewas cooled to 0 C. and treated under an atmosphere of nitrogen and withstirring, with a solution of 8 N chromic acid (prepared by mixing 26 g.of chromium trioxide with '23 cc. of concentrated sulfuric acid anddiluting with Water to 100 cc.), until the color of the reagentpersisted in the mixture. It was stirred for minutes further at 05 C.and diluted with water. The precipitate was collected, washed with waterand dried .under vacuum, thus affording a crude product which uponrecrystallization from acetone-hexane gave 19-methylene-16a,17u-isopropylidenedioxy A pregnen-21-ol-3,11,20- trione acetate(Cpd. No. 45).

The compounds Nos. 38 to 44, inclusive, were treated by the sameprocedure, afiior-ding respectively Cpd. N o:

46. 19-n1ethylene-A -pregnene-170,21-di0l-3,11,20-

trione 21-acetate,

47. 19-methylene l 6a-methyl-A -pregnene-17u,21-

diol-3,11,20-trione 21-acetate,

48. 19-methylene-16fl-methyl-A -pregnene-17a,2;1-

diol-3,11,20-trione ZI-acetate,

49. 19-ethylidene-16a,17a-isopropy1idenedioxy- A-pregnen-21-ol-3,11,20-trione acetate, 50.19-ethylidene-M-pregnened70:,21-diol- 3,11,20-trione i21-acetate,

51. 19-ethylidene-16u-methyl-A -pregnene-1706,21-

diol-3,1 1,20-trione 21-acetate,

52. l 9-ethylidene- 16p-methy1-A -pregnene-17u,21-

diol-3,ll,20-trione Ill-acetate.

Example VII A suspension of 1 g. of 19-methylene-16a,17u-isopro-)ylidenedioxy A preg'nened1,8,21-diol-3,20-dione 21- lcetate (Cpd. No.37) in 60 cc. of methanol was treated vith a solution of 1 g. ofpotassium carbonate in 6 cc. of vater; the mixture was boiled underreflux for 1 hour 1nd then cooled in ice and diluted with water. The?ormed precipitate was collected and recrystallized from 6'. ii?acetonehexane to yield19-methylene-16a,17a-isopropylidenedioxy-N-pregnene-l1fi,21-diol-3,20-dione(Cpd. No. 53).

Following the same procedure there were treated the compounds Nos. 38 to52 inclusive, thus furnishing respectively Cpd. No.:

64. 19-methylene-16/3-methyl-A pregnene 17a,21-'

diol-3 ,1 1,20-trione,

65. 19-ethylidene-16a,17a-isopropylidenedioxy A pregnen-21-ol-3 ,11,20-trione,

66. 19-ethylidene-A -pregnene-17a,21-diol 3,11,20-

trione,

67. 19-ethylidene-16a-methyl-A -pregnene 17oc,21-

diol-3,11,20-trione,

68. 19-ethylidene-16,8-methyl-A -pregnene 170:,21-

diol-3,l1,20-trione.

Example VIII A mixture of 1 g. of19-n1ethylcne-16vt,17a-isopropylidenedioxy-M-pregnene-l1fi,21-diol-3,20-dione(Cpd. No. 53), 4 cc. of pyridine and 2 cc. of propionic anhydride waskept at room temperature overnight, poured into ice water, the formedprecipitate was filtered, washed with Water and dried. Crystallizationwith acetone, hexane gave 19-methylene-16a,17u-isopropylidenedioxy- A-pregnene-11/3,21-diol-3,2O-dione 21-propionate (Cpd. No. 69).

Following the same procedure there were treated the compounds Nos. 54 to68, inclusive, to produce the corresponding 21-propionates.

Example IX To a solution of 5 g. of 19-methylene-A-pregnen-71otol-3,20-dione (Cpd. N0. 19) in cc. of anhydrous benzenethere were added 1 g. of p-toluenesulfonic acid and 10 cc. of aceticanhydride and the mixture was allowed to stand for 24 hours at roomtemperature, poured into ice and water, and the resulting mixturestirred to effect hydrolysis of the excess anhydride. The benzene layerwas separated and washed with 10% sodium carbonate solution and water.Drying, evaporation and crystallization of the residue from ether-hexaneproduced 19-methylene-A -pregnen-17a-ol-3,20-dione acetate (Cpd. No.70).

Following the same procedure there were treated the compounds Nos. 20,21, 26, 27 and 28 thus furnishing respectively Cpd. No.2

71. 19-methylene16oz-methyl-A -pregnen 17a-ol-3,

20-dione acetate,

72. 19-methylene-16,6-methyl-A -pregnen 170L-Ol-3,

20-dione acetate,

73. 19-ethylidene-A pregnen-17ot-ol 3,20 dione acetate.

74. 19-ethylidene-16a-methyl-A -pregnen 17a-ol-3,

20-dione acetate,

75. l9-ethylidene-16fl-methyl-A -pregnen 17OL-O1-3,

20-dione acetate.

Example X 1 g. of 19-methylene-16a,17u-isopr0pylidenedioxy-M-pregnene-3,20-dione (Cpd. N0. 18) was heated on the steam bath with 100cc. of 80% acetic acid under nitrogen for 7 hours, it was thenconcentrated under vacuum to a small volume and poured into water. Theprecipitate was collected, washed well with water, dried andcrystallized from acetone-hexane, thus furnishing 19-methylene-M-pregnene-l6ot,17u-diol-3,20-dione (Cpd. No 76).

The compounds Nos. 25, 53, 57, 61 and 65 were treated by the sameprocedure, thus yielding respectively Cpd. No.:

77. 19-ethylidene-A -pregnene-16a,17a diol 3,20-

dione, 78. 19-methylene-A -pregnene-11B,16x,17a,21 tetrol-3,20-dione,79. 19-ethy1idene-A -pregnene-11,B,16a,17ot,21 tetrol-3,20-dione, 80.19-methylene-A -pregnene-16a,17 x,21 triol 3,

11,20-trione, 81. 19-ethylidene-A -pregnene-16a,17a,21-triol-3 ,11,

ZO-trione.

Example XI The compounds Nos. 76 and 79 were treated in accordance withExample VIII, thus yielding respectively l9-rnethylene-A-pregnene-16a,17u-diol-3,20 dione 16- propionate (Cpd. No. 82) and19-ethylidene-A -pregnene- 11,8,16a,17a,21-tetrol-3,20 dione 16,21dipropionate (Cpd. No. 83).

Example XII The compounds Nos. 76 and 77, were treated in accordancewith Example VIII thus afiording respectively: 19-methylene-A-pregnene-16a,17a-di01-3,20-dione diacetate (Cpd. No. 84) and19-ethy1idene-A -pregnene-1611,1704- diol-3, 20-dione diacetate (Cpd.No. 85).

Example XIII A suspension of 14.5 g. of triphenylphosphonium methylbromide in 250 cc. of anhydrous ether was treated; under an atmosphereof nitrogen, With 40 cc. of a 1 N ethereal solution of butyl lithium andthe mixture was stirred for 2 hours at room temperature. A solution ofg. of 3,20-bis-cycloethylenedioxy-A -101x-pregnen-19al in 100 cc. ofether was then added dropwise in the course of minutes and withstirring. The reaction mixture was stirred for 6 hours further and letstand at room temperature overnight. The ether was displaced with drytetrahydrofuran by distillation and then refluxed for 8 hours. It wasthen cooled, diluted with water and extracted several times with ethylacetate, the organic extract was washed with water, dried over anhydroussodium sulfate and evaporated to dryness. Chromatography of the residueand crystallization of the solid eluates from acetone-hexane gave3,20bis-cycloethylenedioxy- 19-methylene-A -1(la-pregnene (compound No.86).

The starting compounds listed under I (which were obtained in accordancewith preparation 1) were treated by the same procedure thus afiordingthe corresponding products set forth under II.

Com- 1 pound II 3,20-biseyel0cthylenedioxy- 873,ZO-bis-eycloethylenedioxylfia-methyl-A -l0a-pregnen-IQ-mOthylene-IGa-methyl- 19 al. A -10a-pregnene.3,20-bis-cyeloethylenedi0xy- 88 3,ZO-bis-uycloethylonedioxy-ISa-methyl-A -10a-pregnen- 19-methylene-lG/S-methyl- 19-al.M-lOa-pregneno. 3,20-bis-cycloethy1enedioxy- 893,20-bis-cyeloethylenedioxy- 16a,l7a-isopropylidenedi-IQ-methy1ene-16a,17a-isooxy-A 1Oa-pregnen-l9-al.propylidenedioxy-N-10apregnene. 3,20-biscycl0ethylenedioxy- 903,20-bis-eycloethylenedioxy A -lOa-pregnen-l7a-0I-l9-al.19-methy1ene-A-10a-pregnen-17a-ol. 3,ZO-bis-cycloethylenedioxy- 913,ZO-bis-cyeloethylenedioxy- 1(Ba-methyl-A -10a pregnen-19-methylene-16a-mcthy1- 17a-01-l9-21l. M-lOa-pregnen-lM-ol.3,QO-bis-eycloethylenedioxy- 92 3,20-bis-cycloethylenedioxy- IGB-methyLAlua-pregnenl9-methylene-16fl-methy1- 17a-0l-l9-31. A-1Oa-pregnen-17a-ol.

Example XIV The starting compounds of Example XIII were treated inaccordance with the procedure described in that example, except thattriphenylphosphoniurn methyl bromide was substituted bytriphenylphosphonium ethyl bromide thus giving respectively thefollowing final products.

Cpd. No.:

93. 3,20-bis-cycloethylenedioxy-19-etthylidene-A 10a-pregnene,

94. 3,2O-bis-cycloethylenedioxy-19-ethylidene-160cmethyl-M-lOu-pregnene,

95. 3,20-bis-cycloethylenedioxy-19-ethylidene-16B- methyl-A-10u-pregnene,

96. 3,20-bis-cycloethylenedioxy-19-ethylidene-16a,17a-isopropylidenedioxy-A -IOa-pregnene,

97. 3,20-bis-cycloethylenedioxy-l9-ethylidene-A 10ot-pregnen-17a-ol,

98.3,20-bis-cycloethylenedioxy-19-ethylidene-l6ocmethyl-M-lOa-pregnen-17a-pregnen-17u-ol,

99. 3,20-bis-cycloethylenedioxy-l9-ethylidene-16B-methyl-M-lOa-pregnen-l7vt-ol.

Example XV A solution of 5 g. of compound No. 86 in 250 cc. of acetonewas treated with 1 cc. of concentrated hydrochloric acid and the mixturekept at room temperature overnight. It was then poured into water,extracted with methylene chloride and the organic extract washed withwater to neutral, dried over anhydrous sodium sulfate and evaporated todryness. Crystallization from acetone-hexane gave 19-methylene-A-l0ot-pregnene-3,20- dione (Cpd. No.

The compounds Nos. 87 to 99 inclusive, were treated by the sameprocedure, thus affording respectively 1 1 111. 19-ethylidene-A-IOa-pregnen-17ec-ol-3,20-

dione. 1 12. 19-ethylidene-16a-methyl-A -10a-pregnen-17aol-3,20-dione,113. 19-ethylidene-16,B-methyl-A -IOu-pregnen- 17a-ol-3,20-dione.

Example XVI A cooled solution of 4 g. of 19-methy1eI'16-160,170L-lSO-propylidenedioxy-N-10e-pregnene-3,20 dione (Cpd. No. 103) in 30 cc. oftetrahydrofuran and 18 cc. of methanol was treated under continuousstirring with 6 g. of pure calcium oxide, in small portions, and thenwith 6 g. of iodine. The stirring was continued at room temperatureuntil the solution turned pale yellow. The mixture was poured into icewater containing 18 cc. of acetic acid and 2 g. of sodium thiosulfate.After stirring for 15 minutes the solution was decanted and theprecipitate was collected by filtration, thus giving the corresponding21-iodo derivative.

This compound was mixed with 80 cc. of acetone and 12 g. of recentlyfused potassium acetate and the mixture was refluxed for 8 hours,concentrated to small volume, diluted with water and extracted withethyl acetate; the extract was washed with water, dried over anhydroussodium sulfate and concentrated until crystallization started. Theprecipitate was collected and crystallized from methanolwater, thusyielding 19-methylene 160c,170cisopropylidenedioxy-M-lot-pregnen-21-ol-3,20-dione acetate (Cpd. No.114).

The compounds Nos. 104, 105, 106, 110, 111, 112 and 113 were treated bythe same procedure affording respectively Cpd. No.:

115. 19-methylene-A -1Oa-pregnene-17a,21-diol-3,20

dione 21-acetate,

116. l9-methylene-16oz-methyl-A -lOu-pIegnene 17a,

21-diol-3,20-dione ZI-acetate,

117. 19-methylene-16p3-methyl-A -1Oa-pregnene 171x,

21-diol-3,20-dione 21-acetate,

118. 19-ethyliclene-16a,l7a-isopropylidenedioxy A10a-pregnen-2l-ol-3,20-dione acetate,

119. 19-ethylidene-A -10u-pregnene-17a,21-diol-3,20-

dione ZI-acetatc,

120. 19-ethylidene-16a-methyl-A -1Oa-pregnene 17a,

21-diol-3,20-dione 2l-acetate,

121. 19-ethylidene-16fi-methyl-A IOa-pregnene-17a,

21-diol-3,20-dione 21-acetate.

Example XVII The following solutions A, B and C were prepared usingdistilled water as solvent solution A was prepared by mixing 425 cc. ofa 1.742% dipota-ssic phosphate solution, (K HPO with 75 cc. of 1.38%monosodic phosphate; solution B was prepared by diluting a mixture of 1lt. of 4.5% sodium chloride solution, 40 cc. of a 5.75% potassiumchloride solution and 10 cc. of a 10.1% magnesium sulfate, to a volumeof lt. solution C was prepared by dissolving 20.9 g. of fumaric acid and14.4 g. of sodium hydroxide in 1 lt. of water and diluting the solutionto 1.2 lt. Then 475 cc. of solution A, 4.32 lt. of solution B and 1.2lt. of solution C were mixed.

Adrenal glands of recently slaughtered cattle, defatted, were ground ina meat grinder until a homogeneous mass was obtained; to 1 kg. ofhomogenate was added 2 liters of the mixture of A, B and C solutionswith vigorous stirring. To the mixture there was then added 1 g. ofcompound No. 114 dissolved in 5.35 cc. of propylenglycol, the mixturewas stirred at 2837 C. for 3 hours, 13 liters of acetone were added andthe mass was stirred at room temperature for an additional 1 hour.

The acetone extract was separated by filtration, the ground adrenalswere washed with 6 liters of acetone, the extracts were combined and thesolvent removed by distillation under reduced pressure. The residue wastreated with 2 cc. of acetic anhydride and 4 cc. of pyridine for 8hours, then the mixture was worked up conventionally, thus affordingl9methylene-16a,l7et-isopropylidenedioxy-M-lOoc-pregnene-llfi,2l-diol-3,20-dione 2l-acetate (Cpd. No. 122).

The compounds Nos. to 121 inclusive, were treated under the sameconditions, thus yielding respectively Cpd. No.:

123. 19-methylene-A -IOix-pregnene-I1fi,17a,21-triol- 3,20dione21-acetate, 124. 19-methylene-16a-methyl-A -l0a-pregnene-11B,

17u,21-triol-3,20-dione 21-acetate, 125. 19-1nethylene-16/3-methyl-A-1Oa-pregnene-1 lfi,

17a,21-triol-3,20-dione 21-acetate, 126.l9-ethylidene-16a,l7oc-isopropylidenedioxy A4-10ot-pregnene-11fl,21-diol-3,20-dione 21-acetate, 127. 19-ethylidene-A-IOa-pregnene-11,8,17a,21-triol- 3,20-dione 21-acetate,

128. 19-ethylidene-16ot-methyl-A -1Owpregnene-1 l5,

17a,21-triol-3,20-dione 21-acetate,

129. 19-ethylidene-l6,8-methyl-A -IOa-pregnene 11B,

17a,21-triol-3,20-dione 21-acetate.

Example XVIII A solution of 1 g. of compound No. 122 in 10 cc. ofacetone was cooled to 0 C. and treated under an atmos phere of nitrogenand with stirring, with a solution of 8 N chromic acid (prepared bymixing 26 g. of chromium tri-oxide with 23 cc. of concentrated sulfuricacid and diluting with water to 100 cc.), until the color of the reagentpersisted in the mixture. It was stirred for 5 minutes further at 05 C.and diluted with water. The precipitate was collected, washed with waterand dried under vacuum, thus affording a crude product which uponrecrystallization from acetone-hexane gave 19-methylene-16u,17ot-isopropylidenedioxy-A -10a-pregnen-21-ol 3,11,20 trione acetate (Cpd. No.

The compounds Nos. 123 to 129 inclusive, were treated by the sameprocedure, affording respectively Cpd. No.

131. 19-methylene-A -IOa-pregnene-17a,21-diol- 3,1 1,20-trione21-acetate,

132. 19-methylene-1'6u-methyl-A -1Oaregnene- 17a,21-di01-3,l 1,20-trione2 1-acetate,

=133. 19-methylene-16B-methyl-A -1Oaregnene- :,21-(1101-3, 1 1,20-trione21 -acetate,

134. *19-ethylidene-16a,17a-isopropylidenedioxy- A-10a-pregnen-21-ol-3,1 1,20-trione acetate,

135. 19-ethylidene-A -10or-pregnene-17u,2l-diol- 3,11,20-trione21-acetate,

136. 19-ethylidene-16u-methyl-A -10ot-pregnene- 17M,21-dlO1-3,11,20-tri01'1e 21-acetate,

137. 19-ethylidene-16B-methyl-A -lOa-pregnene-'17a,21-diol-3,11,20-trione 21-acetate.

Example XIX A suspension of 1 g. of19-methylene-16a,17x-isopropy1idenedioxy-A-IOa-pregnene-1lfl,21-di0l-3,20-dione 21- acetate (Cpd. No. 122) in 60cc. of methanol was treated with solution of 1 g. of potassium carbonatein 6 cc. of water; the mixture was boiled under reflux for 1 hour andthen cooled in ice and diluted with water. The formed precipitate wascollected and recrystallized from acetone-hexane to yield19-methylene-16u,17a-isopropylidenedioxy-M-lOa-Pregnene-11fi,2'1-diol-3,20-dione(Cpd. No. 13 8).

Following the same procedure there were treated the compounds Nos. 123to 137 inclusive, thus furnishing respectively Cpd. No.:

139. 19-methylene-A -IOu-pregnene-l1fi,17a,21-

triol-3,20-dione,

140. 19-methylene-16a-methyl-A -1Oaregnene- 115,17u,2 l-triol-3,20dione,

' eilect hydrolysis of the excess anhydride.

1 41. 19-methylene-16,8-methy1-A -1Oa-pregnene- 11,8,17a,21-triol-3,20-dione,

142. \19-ethylidene-16u,17ut-isopropylidenedioxy-M- 10wpregnene- 111[3,2 l-diol-3,20-dione,

143. 19-ethylidene-Ah10u-pregnene-I 1,8, 170c,21

triol-3, 20-dione,

144. l9-ethylidene-16a-methyl-A -lOuregnene- 1.15, 17a-21-triol-3,ZO-dione,

145. 19-ethylidene-16B-methyl-A -10u-pregnene- 1:18,17a,21-triol-3,20-dione,

146. 19-methylene-16u,17u-isopropylidenedioxy- A-la-pregnen-2ll-ol-3,11,20trione,

147. 19-methylene-A -IOa-pregnene-17a,21-diol- 3 ,1 1,20-trione,

148. l9-methylene-16a-methyl-A -10a-pregnene-17a,2r1-diol3,11,20-trione,

149. 19-methylene-16B-methyl-A -l0a-pregnene 17a,21-dio1-3,11,20-trione,

150. 19-ethylidene-16a,17a-isopropylidenedioxy- A-10a-pregnen-21-ol-3,11,2O-trione,

151. 19-ethylidene-A -10a-pregnene-17u,21-di0l- 3 ,11,20-trione,

152. 19-et hylidene-16a-methyl-A -10a-pregnene-17a,2/1-diol-3,11,20-trione,

15 3. 19-ethylidene-1 6,8-methyl-A -1Oaregnenel7oc,2 1-diol-3,11,20-trione.

Example XX A mixture of 1 g. of19-methylene-16a,17a-isopropylidenedioxy-M-1-0a-pregnene-1'1/3,21-diol-3,20-dione (Cpd. No. 13 8), 4 cc. of pyridineand 2 cc. of propionic anhydride was kept at room temperature overnight,poured into ice water, the formed precipitate was filtered, washed withwater and dried. Crystallization from acet0ne-hexane gave19-methylene-16a,17a-isopropylidenedioxy-M-lOa-pregnene-I1B,21-diol-3,20-dione 21-propiona-te (Cpd. No. 154).

Following the same procedure there were treated the compounds Nos. 139to 153, inclusive, to produce the corresponding 21-propionates.

Example XXI To a solution of g. of 19-methylene-A -IOu-pregnen-17a-ol-3,20-dione (Cpd. No. 19) in 100 cc. of anhydrous benzene therewere added 1 g. of p-toluenesulfonic acid and 100 cc. of aceticanhydride and the mixture was allowed to stand for 24 hours at roomtemperature, poured into ice and water, and the resulting mixturestirred to The benzene layer was separated and washed with sodiumcarbonate solution and water. Drying, evaporation and crystallization ofthe residue from ether-hexane produced 19-methylene-A-10a-pregnen-17a-ol 3,20 dione acetate (Cpd. No. 155).

Following the same procedure there were treated the compounds Nos. 105,106, 111, 112 and 113 thus furnishing respectively Cpd. N0.:

156. 19-methylene-l6a-methyl-A -10a-pregnen- 17a-ol-3,2.0di-one acetate,

157. 1-9-methylene-165-methyl-A -10u-pregnen- 17a-ol-3,20-dione acetate,

158. 19-ethylidene A -10wpregnen-17ot-ol-3,20-

dione acetate,

9. 19-ethylidene-16a-methyl-A -IOwpregnen- 17o-ol-3,20-dione acetate,

160. 19-ethylidene-16,8-methyl-A -10a-pregnen- 17a-ol-3,20-dioneacetate.

Example XXII 1 g. of 19-methylene-16a,17a-isopropylidenedioxy-A10a-pregnene-3,20-dione (Cpd. No. 10-3) was heated on the steam bathwith 100 cc. of 80% acetic acid under nitrogen for 7 hours,it was thenconcentrated under vacuum to a small volume and poured into water. Theprecipitate 1.4 was collected, washed well with water, dried andrecrystallized from acetone-hexane, thus furnishing l9-methy1ene- A-l0a-pregnene-16u,17ot-diol 3,20-dione (Cpd. No. 16-1). The compoundsNos. 110, 138, 142, 164 and were treated by the same procedure, thusyielding respectively Cpd. N0.:

162. l9-ethylidene-A -10a-pregnene-l6a,17a-diol-3 20-dione,

163. 19-methylene-A -10ot-pregnen-e-1lfi,l6a,17ot,

21 -tetr-ol3 ,20-dione,

164. 19-ethylidene-A -10u-pregnene-11B,l6a,17rz,

2l-tetrol-3,20-dione,

19-met-hylene-A -10a-pregnene-16a,17a,21-

triol-3,1 1,20-trione,

166. 19-ethylidene-A -10a-pregnene-l6u,17a,2l-

triol-3 ,11,20-trione.

Example XXIII The compounds Nos. 161 and 164 were treated in accordancewith Example XX, thus yielding respectively 19-methylene-A-10a-pregnene-16a,l7a-diol 3,20 dione 16-propionate (Cpd. No. 167) andl9-ethylidene-A -10apregnene 11[3,16a,17ot,21-tetrol-3,20-dior1e 16,21dipropionate (Cpd. No. 168).

Example XXIV The compounds Nos. 161 and 162 were treated in accordancewith Example XXI thus affording respectively: 19-methylene-A-10a-pregnene 16oa17u-diol- 3,20 dione diacetate (Cpd. No. 169) and19-ethylidene-A -10a-preg- I'lCIl6-16OL,17OL-dlOl-3,20dl0l'l6 diacetate(Cpd. No. 170).

Example XXV A mixture of 1 g. of 1'9-methylene-A -IOa-pregnene-16a,17u-diol-3,20-dione (Cpd. N0. 161), 50 cc. of freshly distilledacetophenone and 0.5 cc. of 72% perchloric acid was stirred at roomtemperature for 1 hour. The resulting mixture was washed with sodiumbicarbonate solution and with water to neutrality, then it was steamdistilled and the product extracted with methylene chloride. The extractwas dried over anhydrous sodium sulfate and evaporated to dryness.Crystallization from acetone-hexane yielded 19-methylene-A-10a-pregnene-l6a,17rx-diol-3,20- dione 16,17-acetophenonide (Cpd. No.171).

The compounds Nos. 162 and 166 inclusive, were treated by the latterprocedure, thus yielding the corresponding 16,17-acetophenonides.

Example XXVI A solution of 500 mg. of 19-ethylidene-A -10a-p'regnene- 116,16,1711,211tetrol-3,20-dione (Cpd. No. 164) in 20 cc. of chloroformwas treated with l g. of acetaldehyde and a few drops of 3 N perchloricacid and stirred at room temperature for 2 hours. After diluting withwater the chloroform layer was separated, washed with aqueous saturatedsodium bicarbonate solution and then with water, the chloroform wasdistilled and the residue was purified by chromatography on neutralalumina, thus yielding 19- ethylidene-A-10a-pregnene-11,8,16a,17a,21-tetrol 3,20- di'one 16,17-acetaldehydeacetal (Cpd. No. 172).

The compounds Nos. 161, 162, 163, 165 and 166 were treated by the sameprocedure to produce the corresponding 16,17-acetaldehyde acetals.

Example XXVI] yielded 19-methylene-Mpregnene-16u,17a-diol-3,20-dione16,17-acetophenonide (Cpd. No. 173).

Example XX VIII A solution of 500 mg. of 19-ethylidene-A -pregnene- 113,1'6ot,17zx,'2l-i6i IOl-3,20-(1101'16 (Cpd. No. 79) in 20 cc. ofchloroform was treated with 1 g. of acetaldehyde and a few drops of 3 Nperchloric acid and stirred at room temperature for 2 hours. Afterdiluting with water the chloroform layer was separated, washed withaqueous saturated sodium bicarbonate solution and then with water, thechloroform was distilled and the residue was puritied by chromatographyon neutral alumina, thus yielding 19-ethylidene-A-pregnene-11,B,16ot,17a,21 tetrol 3,20- dione16,17-acetaldehyde acetal(Cpd. No. 714).

The compounds Nos. 7 6, 7'7, 78, 80 and 81 were treated by the sameprocedure to produce the corresponding 16, 17-aceta'ldehyde acetals.

I claim:

1. A compound of the following formula:

wherein R is selected from the group consisting of hydrogen, hydroxyland a hydrocarbon carboxylic acyloxy group of less than 12 carbon atoms;T is a member of the group consisting of hydrogen, ot-hydroxy,OL-l'lYdIO- carbon carboxylic acyloxy of less than 12 carbon atoms,u-methyl and ,B-methyl; T and R together are the group X Y '---oRvherein R is hydrogen; T is a member of the group :onsisting ofhydrogen, p -hydroxyl, a-hydrocarbon carboxylic acyloxy of less than 12carbon atoms, a-methyl and fi-methyl; OR and T together are the groupwherein R and R each is a lower alkyl group; Y is selected from thegroup consisting of B-hydroxyl and keto; X is selected from the groupconsisting of hydrogen and a lower alkyl group and R is selected fromthe group consisting of hydrogen and a hydrocarbon carboxylic acyl groupof less than 12 carbon atoms.

13. 19 methylene-M-pregnane-I1/3,17ot,21-triol-3,20- dione 21-aceta te.

14. 19 ethylidene A -pregnene-11fi,17u,21-triol-3,20- dione ZI-acetate.

15. 19 methylene 16a,17ot-isopropylidenedioxy-M-pregnene-l1fl,21-diol-3,20-dione 21-acetate.

16. 19 ethylidene 16a,17ot-isopropylidenedioXy-M-pregnene-l1fi,21-diol-3,20-dione 21-acetate.

17. 19 methylene A -pregnene-17a,21-diol-3,11,20- trione 21-acetate.

18. 19 ethylidene A -pregnene-17ot,21-diol-3,11,20- -trione 21-acetate.

19. 19 methylene 16a,17ot-isopropylidenedioxy-M-pregnene-21-ol-3,11,20-trione acetate.

20. 19 ethylidene 16a,17u-isopropylidenedioxy-A'pregnen-21,-ol-3,11,20-trione acetate.

21. A compound of the following formula:

C I .Qj

wherein R is selected from the group consisting of hydrogen, hydroxyland a hydrocarbon carboxylic acyloxy group of less than 12 carbon atoms;T is a member of the group consisting of hydrogen, ot-hydroxy,a-hyd-rocarbon carboxylic acyloxy of less than 12 carbon atoms,ot-methyl and ,B-methyl; T and R together are the group wherein R and Rare selected from the group consisting of hydrogen and a lowerhydrocarbon residue of up to 8 carbon atoms, and X is a member of thegroup consisting of hydrogen and a lower alkyl group.

22. 19-methylene-A -10a-pregnene-3,20-dione.

23. 19-ethylidene-A -10ot-pregnene-3,20-dione.

24. l9-methyl'ene-A -1Oa-pregnen-17u-ol-3,20-dione.

25. 19-ethylidene-A -1Oa-pregnen-17a-ol-3,20-dione.

26. 19-methylene-16ot,17ot-isopropylidenedioxy-A-l0apregnene-3,20-dione.

27. 19-ethylidene-16a,17ot-isopropylidenedioxy-A-10apregnene-3,20-dione.

28. 19-methylene-l6ot-methyl-A -10ot-pregnen-17ot-ol-3 20-dione.

29. 19 methylene 16B methyl A a pregnen- 17oc-0l-3,20-di0116.

30. 19 ethylidene 16a methyl A 101x pregnen- 17ot-ol-3,20-dione.

CHIzOR 1:0 X Y --o R2 wherein R is hydrogen; T is a member of the groupconsisting of hydrogen, a-hydroxyl, rat-hydrocarbon :carboxylic acyloxyof less than 12 carbon atoms, ot-methyl and ,6- methyl OR and T togetherare the group O R5 wherein R and R are selected from the groupconsisting of hydrogen and a lower hydrocarbon residue of up to 8 carbonatoms; Y is selected from the group consisting of B-hydroxyl and keto; Xis selected from the group consisting of hydrogen and a lower alkylgroup and R is selected from the group consisting of hydrogen and ahydrocarbon carboxylic acyl group of less than 12 carbon atoms.

33. 19 methylene A 10cc pregnene 11,8,17oc,21 triol-3,20-dioneZI-acetate.

34. 19 ethylidene A 10a pregnene 1113,17a,21- triol-3,20-dioneZl-acetate.

35. 19 methylene 16a,17a isopropylidenedioxy- A-10oc-pregnene-1lB,21-dio1-3,2O-dione 2l-acetate.

36. 19 ethylidene 1604,1700 isopropylidenedioxy- A-10a-pregnene-1lfl,21-diol-3,2O-dione 21-acetate.

37. 19 methylene A 10a pregnene 17a,21-diol- 3,11,20-trione 21- acetate.

38. 19 ethylidene A 10a pregnene 17a,21-dio1- 3,1l,20-trione ZI-acetate.

39. 19 methylene 16oz,17oc isopropylidenedioxy-M-lOa-pregnen-Zl-ol-Ll1,20-trione acetate.

44). 19 ethylidene l6a,17a isopropylidenedioxy- A-1Oa-pregnen-2l-ol-3,11,2O-trione acetate.

No references cited.

LEWIS GOTTS, Primary Examiner.

THOMAS M. MESHBESHER, Assistant Examiner.

1. A COMPOUND OF THE FOLLOWING FORMULA: